Silicon dioxide nanoparticles induce anxiety-like behavior in a size-specific manner via the microbiota-gut-brain axis

Abstract

The impacts of silicon dioxide nanoparticles (SiO₂-NPs) on human health have attracted increasing interest due to their widespread utilization in medicine and food additives. However, the size-dependent effects of SiO₂-NPs on brain health remain sparse. Herein we investigated alterations in behavioral patterns, the gut microbiota, inflammation and oxidative stress of mice after a 12-week exposure to SiO₂-NPs with either small size (NP-S) or large size (NP-L). A more pronounced deleterious effect of NP-S was found on anxiety-like behavior in mice relative to NP-L. We also found that SiO₂-NPs exposure induced inflammation and oxidative stress in the colon, hippocampus and cortex of mice in a size-specific manner. Correlation network analysis revealed potential links between anxiety-like behavior and SiO₂-NPs-induced shifts in the gut microbiota including Parvibacter, Faecalibaculum, Gordonibacter and Ileibacterium. Furthermore, anxiety-like behavior caused by SiO₂-NPs exposure exhibited correlations with decreased levels of hippocampal IL-10 and cortex Nqo1 as well as increased levels of intestinal Acox1 and hippocampal TNF-α. Therefore, our findings suggest that exposure to SiO₂-NPs promoted anxiety-like behavior through the mediation of interplay between the gut and the brain, and SiO₂-NPs of smaller size may generate a more adverse effect on brain health.